Monthly intravenous alendronate treatment can maintain bone strength in osteogenesis imperfecta patients following cyclical pamidronate treatment

ObjectivesOsteogenesis imperfecta (OI) is a skeletal dysplasia characterized by recurrent fractures due to congenital bone fragility. The only bisphosphonate approved for OI in Japan is pamidronate (PAM). To investigate whether monthly intravenous alendronate (ALN) infusions can maintain bone strength in OI children following cyclical PAM treatment.MethodsA prospective and non-inferiority study was conducted. Eight school-age OI patients aged 8.5±2.0 years who were treated with cyclical PAM for 6.0±2.3 years were enrolled and switched to monthly intravenous ALN (0.030 mg/kg/month). Changes in L1-4 bone mineral density (BMD) Z-scores, fracture rates, and bone turnover markers for 12 months were analyzed.ResultsAverage BMD Z-scores were −3.0±1.9, −2.9±2.0, and −2.2±2.0 in 12 months before enrollment, at enrollment, and after 12 months of ALN treatment, respectively. BMD Z-scores increased significantly during treatment with both PAM and ALN (p=0.012), and the effect of ALN was not inferior to that of PAM (p=0.67). There was no change in fracture rates (p=0.86) and bone turnover markers during the 12 months before and after enrollment. Additionally, ALN showed no remarkable side effects.ConclusionsOur results suggest that monthly intravenous ALN can maintain bone strength after primary usage of cyclical PAM. We concluded that monthly intravenous ALN as a maintenance treatment following cyclical PAM administration can be an option for OI children.

Effects of bisphosphonate and calcium carbonate on normal aortic valve and cholecalciferol induced in vivo rabbit aortic stenosis model

Background Calcific aortic valve disease (CAVD) is the most common valvular heart disease. Bisphosphonates are stable analogs of pyrophosphates and commonly prescribed in the treatment of osteoporosis. The effects of bisphosphonate treatment on CAVD are not clearly known and there are inconsistent results. Similarly, the effect of calcium supplementation on CAVD remains controversial. Purpose The aim of this study was to assess the effects of bisphosphonate therapy on the normal aortic valve and vitamin D induced in vivo rabbit aortic stenosis (AS) model. Methods The impact of calcium supplementation on the rabbit AS model was also evaluated. A total of 30 New Zealand white rabbits were divided into five equal groups: no treatment (Group I); 25,000 IU/day vitamin D3 (cholecalciferol) (Group II, rabbit AS model); 25,000 IU/day cholecalciferol plus 2500 mg/day calcium carbonate (Group III); 20 μg/kg/week intravenous alendronate (Group IV) and 25,000 IU/day cholecalciferol plus 2500 mg/day calcium carbonate plus 20μg/kg/week alendronate (Group V). Echocardiography was performed at baseline and after 12 weeks of treatment. The left ventricular mass index (LVMI), aortic valve area (AVA), transvalvular velocities and gradients were recorded. Radiologic and histopathologic examination was performed at the end of the 12th week. Control animals displayed no abnormalities of the aortic valve. Results There was no echocardiographic change in Group IV. In Groups II, III and V, there was a significant decrease in AVA and increases in transvalvular velocities and gradients. However, these stenotic changes were significantly prominent in Group V (p=0.001 for all, via repeated measures ANOVA). Moreover, LVMI was only increased in Group V (p<0.05). Calcification of aortic valvar complex was detected in 14 (46.7%) cases by radiologic imaging and 10 (33.3%) cases by histopathologic examination. Most frequent calcification was found in Group V (5 for each method, 83.3%). Agatston, volume and equivalent mass scores of calcific foci in Group V were significantly higher than other groups (p<0.05 for all). There was no significant difference between groups regarding with presence of osteoclasts in calcific foci. Conclusion Calcium supplementation has no effect on the in vivo rabbit AS model. Alendronate treatment aggravates the stenosis and increases the calcification in the rabbit AS model. Alendronate treatment has no effect on the normal valve in which there was no osteogenesis and osteoclastogenesis. Based on these findings, in patients with CAVD, alendronate treatment should be given with regular echocardiographic follow-up or may not be preferred. Central figure Funding Acknowledgement Type of funding source: None

Effect of Abaloparatide vs Alendronate on Fracture Risk Reduction in Postmenopausal Women With Osteoporosis

Context The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed. Objective The objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend. Design In this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend. Results The vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different. Conclusion Initial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.